Long non-coding RNA H19 promotes leukocyte inflammation in ischemic stroke by targeting the miR-29b/C1QTNF6 axis
Guangwen Li, Xiaoqing Ma, Haiping Zhao, Junfen Fan, Tianwei Liu, Yumin Luo, Yunliang Guo, Guangwen Li, Xiaoqing Ma, Haiping Zhao, Junfen Fan, Tianwei Liu, Yumin Luo, Yunliang Guo
Abstract
Aims: Inflammatory processes induced by leukocytes are crucially involved in the pathophysiology of acute ischemic stroke. This study aimed to elucidate the inflammatory mechanism of long non-coding RNA (lncRNA) H19-mediated regulation of C1q and tumor necrosis factor 6 (C1QTNF6) by sponging miR-29b in leukocytes during ischemic stroke.
Methods: H19 and miR-29b expression in leukocytes of patients with ischemic stroke and rats with middle cerebral artery occlusion were measured by real-time polymerase chain reaction. H19 siRNA and miR-29b antagomir were used to knock down H19 and miR-29b, respectively. We performed in vivo and in vitro experiments to determine the impact of H19 and miR-29b on C1QTNF6 expression in leukocytes after ischemic injury.
Results: H19 and C1QTNF6 upregulation, as well as miR-29b downregulation, was detected in leukocytes of patients with stroke. Moreover, miR-29b could bind C1QTNF6 mRNA and repress its expression, while H19 could sponge miR-29b to maintain C1QTNF6 expression. C1QTNF6 overexpression promoted the release of IL-1β and TNF-α in leukocytes, further exacerbated blood-brain barrier disruption, and aggravated the cerebral ischemic injury.
Conclusions: Our findings confirm that H19 promotes leukocyte inflammation by targeting the miR-29b/C1QTNF6 axis in cerebral ischemic injury.
Trial registration: ClinicalTrials.gov NCT03577093.
Keywords: C1QTNF6; inflammation; ischemic stroke; leukocyte.
Conflict of interest statement
The authors declare that they have no competing interests.
© 2022 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.
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Source: PubMed